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PubMedDate not supplied

Sonographic study of postprandial gallbladder emptying and common bile duct changes in patients with diabetes or cholelithiasis.

The aim of our study was to evaluate postprandial emptying of the gallbladder and common bile duct (CBD) in 20 patients with gallstones and in 20 diabetic patients with or without autonomic neuropathy. Gallbladder fasting volume was significantly increased in patients with multiple stones. Diabetics with autonomic neuropathy showed a decreased gallbladder emptying rate. CBD size did not show any significant change in all groups examined.

Autonomic Nervous System Diseases↗
PubMed1992

Indomethacin and postprandial gallbladder emptying.

Patients with gallstone disease commonly have impaired gallbladder emptying. To see whether non-steroidal anti-inflammatory drugs (NSAIDs) prevent gallstone formation by improving gallbladder emptying, we assessed the effect of indomethacin on postprandial emptying in healthy subjects and in patients with gallstone disease. Subjects received indomethacin 25 mg three times a day for a week and matching placebo for another week. Compared with placebo, indomethacin improved postprandial gallbladder emptying in all 7 patients with gallstone disease. This finding was not recorded in healthy subjects with normal gallbladders. The prevention of gallstone formation associated with ingestion of NSAIDs may be due mainly to a prokinetic effect on the gallbladder since there is no evidence to suggest that these drugs affect cholesterol crystal nucleation at ordinary therapeutic doses in man or animals.

Adult↗
PubMed1998

Erythromycin, a motilin agonist, increases postprandial gallbladder emptying during therapy with ursodeoxycholic acid.

Sufficient gallbladder emptying accelerates early gallstone clearance after extracorporeal shock wave lithotripsy (ESWL). Litholytic therapy with ursodeoxycholic acid (UDC) subsequent to ESWL increases fasting volume (FV) and postprandial residual volume (RV) of the gallbladder. This may lead to retention of cholesterol crystals and small fragments within the gallbladder. In order to find out whether erythromycin, a motilin agonist, improves gallbladder emptying, we tested gallbladder motility after administration of ursodeoxycholic acid with and without oral application of erythromycin. Ten healthy males (age 26-35 years) obtained 10 mg/kg/d of UDCA as a single bedtime dose for three weeks. Prior and after UDCA administration, gallbladder FV was determined sonographically after overnight fasting. After a test meal (490 kcal), gallbladder volume was measured every 5 min until the gallbladder had reached its minimal RV. The next day the same procedure was repeated with 500 mg erythromycin p.o. 45 min prior to test meal application. FV, RV, ejection volume (EV = FV-RV) and ejection fraction (EF = EV/FV x 100) were calculated and differences were compared by the student's t-test. FV (29 ml +/- 8 ml vs. 38 ml +/- 10 ml), RV (12 ml +/- 6 ml vs. 17 ml +/- 6 ml) and EV (17 ml +/- 5 ml vs. 21 ml +/- 6 ml) increased significantly during therapy with UDCA (p < 0.05). EF did not change significantly. After erythromycin application RV decreased to its original values (13 ml +/- 6 ml), whereas EV (24 ml +/- 6 ml) and EF (58% +/- 9% vs. 66% +/- 11%) increased significantly (p < 0.05). Thus, administration of a motilin agonist blunts unwanted effects on gallbladder motility during litholytic therapy with UDC.

Administration, Oral↗
PubMedDate not supplied

Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying.

In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.

Adult↗
PubMed1994

Gallbladder emptying after antiulcer gastric surgery.

It has been shown that truncal vagotomy with pyloroplasty (TVP), but not highly selective vagotomy (HSV), delays the onset, decreases the extent, and changes the pattern of gallbladder emptying. The aim of the present study was to investigate any alterations in gallbladder emptying after a variety of antiulcer gastric surgery, by milk-technetium 99m (99mTc)-dimethyl iminodiacetic acid (HIDA) scintigraphy. After excluding the cases with spontaneous gallbladder evacuation before milk ingestion, there were 26 controls, 41 duodenal ulcer (DU) patients, 22 after HSV (15 prospective cases), 50 after TVP (23 prospective cases), 8 after TV with gastrojejunostomy (TV-GJ), 10 after Billroth I gastrectomy, and 29 after Billroth II gastrectomy. None of the patients with gastrectomy had additional vagotomy. TVP significantly delayed the onset and decreased the rate of gallbladder emptying as compared with the control, DU, HSV, and Billroth I groups. TVP also changed the pattern of emptying in 20% of the cases (sequential emptying and refilling events). Antiulcer operations excluding the duodenum (TV-GJ and Billroth II) further reduced the rate of gallbladder emptying as compared with (1) control, DU, HSV, and Billroth I groups (P < 0.0001) and (2) TVP (P < 0.001). Onset of gallbladder emptying was not affected by Billroth II gastrectomy, but was significantly delayed by TV-GJ (P < 0.001). The latter two operations also significantly changed the pattern of gallbladder emptying, exhibiting sequential emptying and refilling events, in most cases (P < 0.01 versus TVP). In conclusion, all antiulcer procedures, except HSV, greatly disturb the pattern, the onset, and the rate of gallbladder emptying. Truncal vagotomy seems to disrupt vagally mediated preduodenal mechanism, resulting in delayed onset and reduced rate, whereas duodenal exclusion by gastrojejunostomy results in severely decreased rate of gallbladder emptying.

Duodenal Ulcer↗
PubMed1994

Gallbladder emptying determines early gallstone clearance after shock-wave lithotripsy.

BACKGROUND/AIMS: Disappearance of gallbladder stones after shock-wave lithotripsy combined with bile acid therapy depends on mechanical evacuation and dissolution of fragments. Many patients with gallstones have impaired gallbladder emptying and may show delayed stone clearance after lithotripsy. METHODS: The effect of gallbladder emptying on gallstone clearance after lithotripsy was prospectively studied in 57 patients with one radiolucent gallbladder stone < or = 20 mm. Gallbladder emptying was assessed sonographically before and after 2 weeks of ursodeoxycholic acid (UDCA) treatment. RESULTS: UDCA increased gallbladder fasting and residual volume and decreased ejection rate but did not affect ejection fraction. Patients with an ejection fraction > 60% achieved complete gallstone clearance after lithotripsy in a higher percentage than patients with smaller ejection fractions (1 month, 31% vs. 7%, P = 0.022; 2 months, 55% vs. 18%, P = 0.003; 3 months, 66% vs. 29%, P = 0.005). Patients who became stone-free within 1 month showed larger ejection fractions than patients with retained fragments (67% +/- 4% vs. 56% +/- 3% before UDCA, P = 0.032; 65% +/- 4% vs. 53% +/- 3% with UDCA, P = 0.017). Further, ejection rate during UDCA therapy was larger in patients with complete gallstone disappearance within 1 month than in patients with delayed fragment clearance (1.57%/min +/- 0.36%/min vs. 0.76%/min +/- 0.09%/min; P = 0.002). CONCLUSIONS: Gallbladder emptying is a major determinant of early gallstone clearance after lithotripsy.

Adult↗
PubMed1994

Effect of erythromycin on gastric and gallbladder emptying and gastrointestinal symptoms in scleroderma patients is maintained medium term.

OBJECTIVES: Scleroderma patients frequently present esophageal and gastric emptying abnormalities and small bowel dysfunction. Erythromycin, a macrolide antibiotic, has been found to accelerate gastric and gallbladder emptying in both healthy subjects and diabetic patients. Our objective was to investigate the effects of 4-wk oral erythromycin administration on the gastric and gallbladder emptying, gastrointestinal symptoms (early satiety, abdominal pain, nausea, bloating, vomiting, and constipation), and motilin plasma levels of patients with scleroderma. METHODS: 12 scleroderma patients were investigated before and after 4-wk treatment with 250 mg oral erythromycin three times a day. The effect of a single i.v. dose of 2 mg/kg/h erythromycin on gastric and gallbladder emptying before starting the oral treatment was also evaluated. Gastric and gallbladder emptying after a solid meal were evaluated by sonography. RESULTS: Single i.v. administration of erythromycin before the meal reduced gastric emptying T1/2 from 121.3 +/- 14.0 to 45.5 +/- 7.3 min (p < 0.01) and accelerated gallbladder emptying without affecting the peak. Four-week oral administration of erythromycin reduced gastric emptying T1/2 from 121.3 +/- 14.0 min to 46.5 +/- 8.3 min (p < 0.01). Peak gallbladder emptying was also significantly accelerated, while total emptying remained unchanged (p < 0.01). Furthermore, 4-wk erythromycin administration reduced both motilin plasma levels (from 223.4 +/- 53.8 to 145.4 +/- 67.2 pmol/L, p < 0.01) and symptoms of nausea, vomiting, and abdominal pain (p < 0.01), and increased bowel movements in a subset of scleroderma patients with intestinal pseudo-obstruction. CONCLUSIONS: Erythromycin stimulates gastrointestinal motility in patients with scleroderma. Administered medium-term, it accelerates gastric and gallbladder emptying and alleviates gastrointestinal symptoms.

Drug Administration Schedule↗
PubMed1990

Duodenal osmolality drives gallbladder emptying in humans.

The effect of duodenal osmoreceptor stimulation on gallbladder motility was evaluated in 18 normal subjects during intraduodenal infusion of 280, 560 and 840 mosm/liters NaCl solutions. Gallbladder emptying was found to be dose-dependent between 560 and 840 mosm/liter (P less than 0.01 vs basal volume). The effect of duodenal infusion of hypertonic saline on gallbladder emptying was prevented by atropine and partially antagonized by naloxone, indicating that cholinergic and endorphinergic pathways may be involved in regulating this reflex. Since proglumide, a cholecystokinin (CCK) antagonist, did not affect gallbladder emptying induced by hypertonic saline, it seems likely that CCK is not released by increasing duodenal osmolality. A significant reduction in gallbladder volume was obtained when hyperosmolar saline was delivered into the duodenum, whereas no emptying was seen when infused into the gastric antrum or the jejunum, suggesting that osmoreceptors that activate gallbladder emptying are located only in the duodenum. Additionally, all subjects manifested central symptoms (nausea or vomiting) during duodenal infusion of hypertonic saline, suggesting that central mechanisms might be activated by a change in duodenal osmolality. Our data indicate that the osmolality of duodenal contents might regulate gallbladder motility by neural atropine- and naloxone-sensitive pathways.

Adult↗
PubMed1995

[Study on CCK-induced gallbladder emptying with real-time ultrasonography].

In the present study, we adopted real-time ultrasonography to investigate the effect of atropine on the gallbladder emptying induced by CCK-OP in the normal subjects, and the difference of gallbladder emptying induced by CCK-OP between the "silent" gallstone patients and the controls. The results showed that: (a) CCK-induced gallbladder emptying in normal subjects was inhibited from 88.7% +/- 5.5% without atropine to 43.4% +/- 9.4% with atropine (P < 0.001). (b) The fasting gallbladder volume in the "silent" gallstone patients (26.7 +/- 10.9cm3) was significantly larger than that in the control (19.2 +/- 7.3cm3) (P < 0.05) and gallbladder emptying in the "silent" gallstones patients (44.0% +/- 8.7%) was significantly lower than that in the control (53.4% +/- 6.4%) (P < 0.01). We concluded that, significantly inhibited CCK-induced gallbladder emptying and there was significantly impaired gallbladder emptying in the patients with gallstones.

Adult↗
PubMed1985

Cholinergic effects on gallbladder emptying in humans.

The role of cholinergic mechanisms in the control of gallbladder emptying has not been defined. In this report a scintigraphic technique using 2,6-dimethylphenylcarbamoylmethyl iminodiacetic acid labeled with technetium 99m to visualize the gallbladder and its emptying and diethylenetriamine pentaacetic acid labeled with indium 111 to visualize the stomach and its emptying was used to study 43 normal subjects and 18 patients with vagotomies. Direct cholinergic stimulation with bethanechol induced significant gallbladder emptying. Cholinergic blockade with atropine sulfate decreased the gallbladder emptying responses to a liquid meal, a solid meal, and the infusion of cholecystokinin-octapeptide. In patients with vagotomies, gallbladder emptying was decreased despite accelerated gastric emptying of an ingested liquid meal. The gallbladder emptying response to cholecystokinin-octapeptide was augmented in patients who had undergone vagotomy. These studies suggest that cholinergic receptors may be important in the regulation of human gallbladder emptying.

Adult↗
PubMed1983

Coordination of gastric and gallbladder emptying after ingestion of a regular meal.

The relationship of gallbladder emptying and refilling to gastric emptying of solids, gastrointestinal transit time, and human pancreatic polypeptide response was examined after ingestion of a standard breakfast (40% fat) in 12 healthy men and women. Gallbladder volume, emptying, and refilling was measured by real-time ultrasonography, and gastric emptying of solids was measured scintigraphically by the disappearance from the stomach of egg labeled with 99mTc-sulfur colloid. Gastrointestinal transit time was defined as the time of initial rise in breath hydrogen following ingestion of 10 g of lactulose. Serum human pancreatic polypeptide level was measured by radioimmunoassay. Gallbladder emptying was biphasic, initially 0.015 +/- 0.003 min-1 and later 0.005 +/- 0.001 min-1, and gallbladder volume remained small until refilling began at 249 +/- 67 min. Gallbladder refilling was 70% complete at 335 +/- 57 min. The slower rate of gallbladder emptying and tonic gallbladder contraction occurred during gastric emptying of solids. Gallbladder refilling began when approximately 13% of solids remained in the stomach. Serum human pancreatic polypeptide showed the expected biphasic response to the meal and returned to basal levels at approximately the time of initiation of gallbladder refilling. The gastrointestinal transit time of women was twice that of men (73.6 +/- 20.2 vs. 37.5 +/- 22.7, p = 0.025). No other sex-related differences were detected. We conclude that gastric emptying of the solid portion of a meal containing fat maintains tonic gallbladder contraction through continued release of humoral mediators from small bowel and pancreas. When gastric emptying nears completion, humoral stimulation ceases and the gallbladder refills. Human pancreatic polypeptide does not appear to be responsible for gallbladder refilling.

Adult↗
PubMed2001

Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones.

BACKGROUND AND AIM: Biliary cholesterol supersaturation, gallbladder stasis and delayed intestinal transit are the key events in cholesterol gallstone formation. We studied the effect of cisapride, a prokinetic drug, on gallbladder emptying and bile composition in patients with gallstone disease undergoing cholecystectomy. METHODS: Gallbladder emptying, cholesterol saturation index (CSI) and nucleation time were studied in 21 patients with gallstone disease. Eleven patients (cisapride group, age 41.9 +/- 2.9 years) received tablet cisapride 10 mg t.i.d. for 2 weeks, while 10 patients (placebo group, age 42.1 +/- 1.9 years) received placebo for the same duration. Gallbladder emptying was repeated in all patients after a 2-week treatment with cisapride or placebo. Gallbladder bile was obtained at the time of surgery for the measurement of CSI and nucleation time. RESULTS: Residual volume of the gallbladder decreased (mean +/- SE, 18.6 +/- 2.5 mL vs 10.0 +/- 1.1 mL, P = 0.007), and the ejection fraction increased (43.5 +/- 5.3% vs 60.0 +/- 3.2%, P = 0.007) in patients in the cisapride group, while no change was observed in placebo group patients. Nucleation time was higher in the cisapride group than in the placebo group (14.9 +/- 1.3 days vs 8.0 +/- 0.9 days, P = 0.003). Patients in the cisapride group had a significantly lower cholesterol concentration (molar percentage, 5.1 +/- 0.3% vs 6.8 +/- 0.8%, P = 0.049) and CSI (1.0 +/- 0.1 vs 1.36 +/- 0.11, P = 0.034) than patients in the placebo group. CONCLUSION: Cisapride improves gallbladder emptying and bile lithogenicity in patients with gallstone disease.

Adult↗
PubMed2002

Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects.

Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5+/-10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7+/-8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student's t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin (P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.

Journal Article↗
PubMed1993

5-hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin.

In the present study we evaluated the effect of ondansetron (formerly indicated as GR38032F), a potent and selective type-3 5-hydroxytryptamine receptor antagonist, on erythromycin-induced gallbladder emptying and motilin release, as well as gallbladder emptying induced by a regular meal in healthy volunteers. Gallbladder emptying was evaluated by sonography. Ondansetron, at the dose of 0.05 mg/kg, significantly reduced (P < 0.001 by ANOVA) the gallbladder emptying induced by 2 mg/kg/hr erythromycin, but did not increase basal gallbladder volume or inhibit gallbladder emptying induced by a regular meal. Ondansetron also inhibited the motilin release induced by erythromycin (P < 0.001, by ANOVA). These results suggest that serotoninergic mechanisms modulate the effects of erythromycin on the gastrointestinal tract. The exact site of action of ondansetron remains to be identified.

Adult↗
PubMed1995

Increases in plasma motilin follow each episode of gallbladder emptying during the interdigestive period, and changes in serum bile acid concentration correlate to plasma motilin.

BACKGROUND: The relationship between each single period of gallbladder emptying during the migrating motor complex (MMC) cycle and changes in concentration of plasma motilin and serum bile acids is unknown. METHODS: The variations in the concentration of plasma motilin and serum bile acids in relation to interdigestive gallbladder motility and the MMCs was studied in nine healthy male volunteers. A method combining biliary scintigraphy (99mTc-labelled dimethyl-iminodiacetic acid) and continuous pressure recording from the antroduodenal region was used. RESULTS: During 9 MMC cycles a total of 15 episodes of gallbladder emptying were observed with a median (range) duration of 25 min (15-45 min). Each episode of gallbladder emptying was followed by a steep increase in plasma motilin, reaching a median value of 30 pmol/l (13-43 pmol/l), corresponding to an increase of 18 pmol/l (4-33 pmol/l). The increase in plasma motilin started at the beginning of gallbladder emptying, but the peak value was not reached until a median of 20 min (10-45 min) later. Low plasma motilin concentrations were found between the emptying periods in cases with two or more emptying during the MMC cycle. The serum concentration of bile acids also showed a cyclic variation in relation to gallbladder motility. During periods of gallbladder emptying serum bile acid concentration had a median value of 1.78 mumol/l, as compared with a median value of 1.17 mumol/l during periods of gallbladder filling. This difference did not reach significance, however. In the pooled data from all subjects, a significant correlation (p < 0.01) between the serum concentration of bile acids and plasma concentration of motilin was found. CONCLUSION: Gallbladder emptying was followed by a steep increase in plasma motilin concentration, and in cases of two or more emptying periods during the MMC cycle the concentration decreased in between. The shape of the serum bile acid profile is dependent on the intestinal transport and absorption of bile acids, and the significance of the cyclic variation in serum concentration of bile acids in relation to plasma motilin, gallbladder motility, and MMC needs further investigation.

Adult↗
PubMed1995

Gallbladder emptying in vivo, bile composition, and nucleation of cholesterol crystals in patients with cholesterol gallstones.

BACKGROUND/AIMS: Impaired postprandial gallbladder emptying may provide time for progressive bile concentration with formation of instable cholesterol-rich vesicles and fast nucleation of cholesterol crystals. The aim of this study was to assess postprandial gallbladder emptying, bile composition, and nucleation of cholesterol crystals in the same patient. METHODS: In 30 patients with cholesterol gallstones, postprandial gallbladder emptying was measured ultrasonographically. In each patient, gallbladder bile composition (obtained at cholecystectomy) and nucleation of cholesterol crystals was determined. Patients were divided in 22 strong contractors (> 50% postprandial gallbladder emptying) and 8 weak contractors. RESULTS: In weak contractors, bile salt and phospholipid concentrations were much higher than in strong contractors (234.6 +/- 24.7 vs. 130.3 +/- 10.8 mmol/L [P < 0.001] and 44.5 +/- 3.5 vs. 30.2 +/- 3.1 mmol/L [P < 0.05], respectively). Cholesterol concentrations were comparable in strong and weak contractors. Consequently, total lipid concentration was significantly higher (15.5 +/- 1.4 and 9.2 +/- 0.7 g/dL; P < 0.001) and cholesterol saturation index significantly lower (0.90 +/- 0.08 and 1.61 +/- 0.17; P < 0.001) in weak contractors. Nucleation time, percentage of cholesterol in vesicles, bile salt species, and molecular species of phosphatidylcholine were not significantly different. CONCLUSION: Differences in bile composition can be linked to different patterns of postprandial gallbladder emptying and may point to two different pathways of gallstone formation.

Adult↗
PubMed1998

Effect of oral cisapride on gallbladder emptying during fasting and postprandial states.

RATIONALE AND OBJECTIVES: The purpose of the study was to determine the effect of orally administered cisapride on gallbladder emptying in healthy subjects during fasting and postprandial states. MATERIALS AND METHODS: Gallbladder emptying was assessed by means of ultrasonography in 10 healthy male subjects (age range, 25-33 years; mean age, 28.6 years +/- 3.2 [standard deviation]) under four randomly applied conditions: (a) after oral intake of a placebo tablet, (b) after oral intake of 10 mg of cisapride during fasting, (c) after oral intake of a placebo tablet followed 30 minutes later by ingestion of 300 mL of fresh whole milk (postprandial emptying), and (d) after oral intake of 10 mg of cisapride followed 30 minutes later by ingestion of 300 mL of milk. RESULTS: Cisapride given during the fasting state induced gallbladder contraction by 44.1% +/- 12.6 (standard deviation) of its initial volume. Gallbladder emptying started after 19.4 minutes +/- 12.6 and reached its peak 51 minutes +/- 5.7 later. The ejection fraction after administration of only cisapride was significantly less than that after placebo and milk ingestion (44.1% +/- 12.6 vs 60.6% +/- 8.5, P < .0002). Oral administration of cisapride 30 minutes before milk consumption induced gallbladder emptying, which started approximately 10 minutes before milk ingestion. The ejection fraction after administration of cisapride with milk was significantly greater than that after consumption of placebo and milk (67.1% +/- 8.8 vs 60.6% +/- 8.5, P < .02). CONCLUSION: Oral cisapride induces contraction of the gallbladder during the fasting state and enhances postprandial gallbladder emptying.

Administration, Oral↗
PubMed1995

Inhibition of gallbladder emptying decreases cholesterol saturation in bile in the Richardson ground squirrel.

Impaired gallbladder emptying is frequent in cholesterol gallstone disease as well as in predisposing conditions like pregnancy and obesity. Gallbladder hypomotility is considered a pathogenic factor for gallstone formation, providing the residence time for cholesterol crystal nucleation, but any effect on the enterohepatic circulation of bile acids and subsequently on biliary lipid composition is unknown. Therefore, we studied the effect of prolonged suppression of gallbladder emptying with a cholecystokinin (CCK-A) receptor antagonist on bile formation in Richardson ground squirrels fed a trace versus a 1% cholesterol diet. Biliary lipid secretion was measured directly and bile acid pool size assessed by isotope dilution ([14C]-cholic acid). Gallbladder contraction was determined in vitro in response to CCK. The CCK-antagonist (MK-329) greatly inhibited gallbladder contraction in vitro and increased gallbladder fasting volume and bile acid pool size in vivo. It significantly lowered the cholesterol saturation index by 35% and 46% in hepatic bile and by 18% and 28% in gallbladder bile in the trace and cholesterol diet groups, respectively. Bile acid secretion and bile flow doubled with the CCK-receptor antagonist. Chronic CCK receptor antagonist-induced inhibition of gallbladder emptying increases bile acid secretion and thereby decreases cholesterol saturation in bile. Extensive biliary hypomotility thus leads to a more rapid cycling of bile acids by depriving the gallbladder of its function in the enterohepatic circulation.

Animals↗